Milan are missing five players with COVID-19 and have a completely revamped defence, while Roma welcome back Lorenzo Pellegrini with Tammy Abraham.
It kicks off at San Siro at 17.30 GMT, you can follow all the build-up and action as it happens from today’s Serie A games on the LIVEBLOG.
The Rossoneri start 2022 the same way they ended 2021, with Stefano Pioli picking a team from whoever is left in the squad.
This time, he had five players ruled out by COVID-19 – Fikayo Tomori, Davide Calabria, Alessio Romagnoli, Samu Castillejo and Ciprian Tatarusanu.
Meanwhile, Franck Kessie, Ismael Bennacer and Fode Ballo-Toure were on Africa Cup of Nations duty, with Simon Kjaer, Pietro Pellegri and Alessandro Plizzari injured.
Roma have their fair share of issues too, as Borja Mayoral and Daniel Fuzato have COVID-19, with Amadou Diawara and Ebrima Darboe at the Africa Cup of Nations, Leonardo Spinazzola injured.
The good news for Jose Mourinho is the return of Pellegrini after a long lay-off, supporting Nicolò Zaniolo and Tammy Abraham, while Rui Patricio can play despite a back issue.
Milan: Maignan; Florenzi, Gabbia, Kalulu, Theo Hernandez; Tonali, Krunic; Messias, Brahim Diaz, Saelemaekers; Giroud
Roma: Rui Patricio; Mancini, Smalling, Ibanez; Karsdorp, Mkhitaryan, Veretout, Pellegrini, Vina; Zaniolo, Abraham